PROJECT SUMMARY - OVERALL The overall goal of the University of Michigan Skin Biology and Diseases Resource-based Center (UM- SBDRC) is to leverage our strengths in genomic editing, bioinformatics and mouse modelling to enable rapid transition from discovery to function, address biological and disease context, and facilitate development of appropriate state-of-the-art in silico approaches and in vivo mouse models of disease. A major emphasis of the UM-SBDRC is to apply years of cutting-edge mouse modeling expertise to the study of inflammatory skin disease using new knowledge gained through big-data approaches. Thus, the UM-SBDRC will both facilitate and accelerate ongoing research towards new discoveries and ultimately benefit a wide range of patients with cutaneous disorders. Two Resource Cores will be established within the UM-SBDRC: they will enhance efficiency and translational impact of cutaneous research; provide access to unique resources and expertise; facilitate new discoveries; and provide training and guidance regarding experimental design and analysis. In addition, the Resource Cores will continuously innovate to maintain our research at the forefront of the field. The Functional Analytics Core will provide unique and innovative, state-of-the art services for CRISPR/Cas9 mutagenesis in keratinocytes, with transcriptomic and epigenomic profiling of genetically-altered keratinocytes, and integration into a systems biology pipeline for data analysis and interpretation. This core will also provide UM-SBDRC members direct access to our bioinformatics resources and to large-scale genomic and transcriptomic datasets of human skin disease through a searchable web-based interface. The Animal Modeling Core will provide services for the design, development, validation, and characterization of genetically-engineered mouse models (GEMMs) to aid in the functional validation of results generated in the Functional Analytics Core. The Animal Modeling Core will also provide resources and guidance for GEMM phenotyping and in vivo manipulation, including transgene induction protocols, UV irradiation, inflammation and fibrosis models, and for establishment of cell cultures from GEMMs. The Administrative Core will provide leadership, oversight and structure for the UM-SBDRC and build and administer a robust Enrichment Program, which includes a Mentoring Program, Pilot & Feasibility Program, Travel Awards, Visiting Speaker Series, and an Annual Symposium, with strong institutional and departmental support for the Center. In summary, UM-SBDRC will provide sophisticated infrastructure and state-of-the-art resources, expertise, and training opportunities at Michigan. This new Center is in line with the NIAMS mission to provide critical research infrastructure, pooled facilities, services and resources to groups of investigators conducting research on skin biology and diseases. The UM-SBDRC will enrich and enhance effectiveness of ongoing basic and translational research, help bring outside investigators into the field of cutaneous biology, broaden the scope of skin research, and accelerate new discoveries to ultimately benefit patients with a wide range of skin diseases.